Development Of Withdrawal Symptoms Research Articles

Reducing the Risk of Withdrawal Symptoms and Relapse Following Clozapine Discontinuation-Is It Feasible to Develop Evidence-Based Guidelines?

Clozapine is the only antipsychotic that is effective in treatment-resistant schizophrenia. However, in certain clinical situations, such as the emergence of serious adverse effects, it is necessary to discontinue clozapine. Stopping clozapine treatment poses a particular challenge due to the risk of psychotic relapse, as well as the development of withdrawal symptoms. Despite these challenges for the clinician, there is currently no formal guidance on how to safely to discontinue clozapine. We assessed the feasibility of developing evidence-based recommendations for (1) minimizing the risk of withdrawal symptoms, (2) managing withdrawal phenomena, and (3) commencing alternatives treatment when clozapine is discontinued. We then evaluated the recommendations against the Appraisal of Guidelines for Research and Evaluation (AGREE) II criteria. We produced 19 recommendations. The majority of these recommendation were evidence-based, although the strength of some recommendations was limited by a reliance of studies of medium to low quality. We discuss next steps in the refinement and validation of an evidence-based guideline for stopping clozapine and identify key outstanding questions.

Feasibility and acceptability of a randomized controlled trial to investigate withdrawal symptoms in response to caffeinated sugary drink cessation among children

BackgroundSugary drinks (SDs) are key contributors to excess added sugar intake and the predominant source of caffeine among children. Chronic caffeine intake causes dependence, and evidence for sugar dependence is emerging. Development of withdrawal symptoms may pose an obstacle to SD cessation among children. We examined the feasibility and acceptability of a three-arm randomized controlled trial (RCT) designed to investigate withdrawal symptoms resulting from replacement of children's usual caffeinated SD intake with either caffeine-free alternatives or caffeine-free and sugar-free alternatives, compared with continued consumption of caffeinated SDs. MethodsTwenty-nine children 8–12 years old, who consumed ≥12 ounces caffeinated SDs daily, enrolled. The two-week RCT required three in-person meetings and daily completion of electronic questionnaires to assess withdrawal symptoms and intervention adherence. Children were randomized to replace their usual caffeinated SD consumption with 1) caffeine-free alternatives, 2) caffeine-free and sugar-free alternatives, or 3) caffeinated SDs (control), provided by the study team. Feasibility and acceptability were assessed quantitatively and qualitatively. ResultsTwenty-eight participants (97%) completed the study. Adherence was high, with 73% reporting compliance with beverage assignments, and 76% completing all questionnaires. In qualitative interviews at follow-up, children described feelings of importance and commitment, and parents did not find the procedures to be overly burdensome. While challenges to adherence were reported (e.g., child wanting other SDs, time commitment), participants described innovative strategies (e.g., designating a place for study drinks in the refrigerator) to maintain adherence. ConclusionResults indicated high levels of RCT feasibility and acceptability. The reported barriers and strategies for adherence will inform modifications required to design a larger and longer-term trial investigating withdrawal symptoms after SD cessation in children.

The association between interleukin-8 levels and the development of withdrawal symptoms during methamphetamine abstinence.

Withdrawal symptoms are common during methamphetamine (METH) abstinence. This study aimed to explore the association between serum interleukins and withdrawal symptoms during METH abstinence. This study recruited 120 METH users, and 94 of them completed the 2-week follow-up. Serum interleukin-1β, 6,8,10 were tested at admission. Withdrawal symptoms were assessed by the Methamphetamine Withdrawal Questionnaire (MAWQ). Serum IL-8 levels were positively correlated with MAWQ scores at the 2-week endpoint (r = .257, p = .013). The variation of the MAWQ scores during the 2-week follow-up was negatively correlated with serum IL-8 levels at admission (r = -.249, p = .026). Serum IL-8 levels remained associated with the severity of METH withdrawal symptoms (β = .363, p = .023), after adjusting for potential confounders. This study did not include normal controls. Most patients were male and cigarette smokers. Patients were only followed up for 2 weeks, and their toxicology data were not collected. Interleukins were only measured at admission, and were tested in serum, not in the cerebrospinal fluid. Our study demonstrated that higher serum IL-8 levels may predict more severe withdrawal symptoms at 2 weeks after METH abstinence.

Khat withdrawal symptoms among chronic khat users following a quit attempt: An ecological momentary assessment study.

Research reports show increased prevalence of habitual khat chewing among various parts of the community in Ethiopia. Some users experience problems controlling their use; withdrawal symptoms may be adding to difficulties with reducing or ceasing use. We aimed to describe the nature and the time course of any withdrawal syndrome in relation to the cessation of khat use over the first 2 weeks of a quit attempt. Fifty-nine participants between the ages of 18 and 35 and who have already chewed ≥1 bundle of khat in their life with a chewing frequency of ≥3 days per week were recruited from Adama Science and Technology University campus. Participants were predominantly male (n = 45, 75%) and had the mean age of 24.8 years (range = 20-32; SD = 2.8). Participants used smart phones to monitor withdrawal symptoms and cravings. The total assessments were divided in to 3 prequit and 14 postquit days. The development of withdrawal symptoms was evident, and all withdrawal symptoms followed similar overall patterns, with salient elevations after the quit day and curvatures around the first week of postquit period. Depression, craving, nervousness, tiredness, restlessness, poor motivation, irritability, and negative affect substantially increased and reached peak on the first week around Day 7 and remained higher compared with the level at baseline indicating the persistence and severity of these symptoms over time. In addition, craving, irritability, and restlessness had significantly reverted to their baseline level during the second week of the postquit duration. We have demonstrated low rates of success during unaided quite attempts from khat and that the withdrawal syndrome is not trivial. Interventions are necessary to support individuals during the period of increased symptoms of dysphoria and to reduce the risk of relapse. (PsycINFO Database Record

The use of selective serotonin receptor inhibitors (SSRIs) is not associated with increased risk of endoscopy-refractory bleeding, rebleeding or mortality in peptic ulcer bleeding.

Observational studies have consistently shown an increased risk of upper gastrointestinal bleeding in users of selective serotonin receptor inhibitors (SSRIs), probably explained by their inhibition of platelet aggregation. Therefore, treatment with SSRIs is often temporarily withheld in patients with peptic ulcer bleeding. However, abrupt discontinuation of SSRIs is associated with development of withdrawal symptoms in one-third of patients. Further data are needed to clarify whether treatment with SSRIs is associated with poor outcomes, which would support temporary discontinuation of treatment. To identify if treatment with SSRIs is associated with increased risk of: (1) endoscopy-refractory bleeding, (2) rebleeding or (3) 30-day mortality due to peptic ulcer bleeding. A nationwide cohort study. Analyses were performed on prospectively collected data on consecutive patients admitted to hospital with peptic ulcer bleeding in Denmark in the period 2006-2014. Logistic regression analyses were used to investigate the association between treatment with SSRIs and outcome following adjustment for pre-defined confounders. Sensitivity and subgroup analyses were performed to evaluate the validity of the findings. A total of 14 343 patients were included. Following adjustment, treatment with SSRIs was not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] [95% Confidence Interval (CI)]: 1.03 [0.79-1.33]), rebleeding (OR [95% CI]: 0.96 [0.83-1.11]) or 30-day mortality (OR [95% CI]: 1.01 [0.85-1.19]. These findings were supported by sensitivity and subgroup analyses. According to our data, treatment with SSRIs does not influence the risk of endoscopy-refractory bleeding, rebleeding or 30-day mortality in peptic ulcer bleeding.

A comprehensive overview on Kratom

Kratom (Mitragyna speciosa Korth) is a tropical tree, indigenous to South East Asia. Historically, the plant is locally used as a stimulant, a remedy in traditional medicine and in social context. Imported to Western countries, Kratom is classified as a novel psychoactive substance (NPS). A systematic review of the literature on Mitragyna speciosa and its main constituents was carried by our international multidisciplinary group. Results were qualitatively analysed in three main areas of interest: in-vitro and preclinical data on pharmacology and behavioral effects, laboratoristic techniques for identification/characterization, epidemiological/toxicological reports on humans. At present, there is no systematic data on the prevalence of Kratom use in all the native countries, but it seems to be considerable. In South-East Asia, Kratom, even if banned, might be still considered a better option than other illicit drugs, an alternative opioid treatment, a natural remedy with no real social stigma attached to its consumption. In parallel, this ethno-drug seems to be popular in Western countries, largely unregulated, easily available on the Internet. Kratom pharmacology appears to be complex, with many alkaloids involved. The subjective effects in humans are very peculiar and seem to be dose-dependent, ranging from psycho-stimulant to sedative-narcotic. Available data on Kratom suggest caution: this psychoactive plant could exhibit a serious harmful potential. Kratom use seems to be associated with drug dependency, development of withdrawal symptoms, craving, serious adverse effects and life-threatening effects in a multidrug-intoxicating scenario. On the other hand, its anxyiolitic, antidepressant and analgesic properties deserve to be further studied.

Acute and chronic ethanol exposure differentially regulate CB1 receptor function at glutamatergic synapses in the rat basolateral amygdala

The endogenous cannabinoid (eCB) system has been suggested to play a key role in ethanol preference and intake, the acute effects of ethanol, and in the development of withdrawal symptoms following ethanol dependence. Ethanol-dependent alterations in glutamatergic signaling within the lateral/basolateral nucleus of the amygdala (BLA) are critical for the development and expression of withdrawal-induced anxiety. Notably, the eCB system significantly regulates both glutamatergic and GABAergic synaptic activity within the BLA. Chronic ethanol exposure significantly alters eCB system expression within regions critical to the expression of emotionality and anxiety-related behavior, including the BLA. Here, we investigated specific interactions between the BLA eCB system and its functional regulation of synaptic activity during acute and chronic ethanol exposure. In tissue from ethanol naïve-rats, a prolonged acute ethanol exposure caused a dose dependent inhibition of glutamatergic synaptic activity via a presynaptic mechanism that was occluded by CB1 antagonist/inverse agonists SR141716a and AM251. Importantly, this acute ethanol inhibition was attenuated following 10 day chronic intermittent ethanol vapor exposure (CIE). CIE exposure also significantly down-regulated CB1-mediated presynaptic inhibition at glutamatergic afferent terminals but spared CB1-inhibition of GABAergic synapses arising from local inhibitory-interneurons. CIE also significantly elevated BLA N-arachidonoylethanolamine (AEA or anandamide) levels and decreased CB1 receptor protein levels. Collectively, these data suggest a dynamic regulation of the BLA eCB system by acute and chronic ethanol.

Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users

BackgroundKratom (Mitragyna speciosa) preparations have been traditionally used in Southeast Asia for its medicinal properties. Lately, Kratom use has spread to Europe and the US, where abuse potential and health hazards increasingly emerge. This study is the first to measure systematically Kratom dependence, withdrawal symptoms, and drug craving in regular Kratom users in Malaysia. MethodsA cross-sectional survey of 293 regular Kratom users was conducted in the community across three northern peninsular states of Malaysia. The Leeds Dependence Questionnaire, Marijuana Withdrawal Checklist, and Marijuana Craving Questionnaire-Short Form were used to measure Kratom dependence, withdrawal and craving. ResultsMore than half of the regular users (>6 month of use) developed severe Kratom dependence problems, while 45% showed a moderate Kratom dependence. Physical withdrawal symptoms commonly experienced include muscle spasms and pain, sleeping difficulty, watery eyes/nose, hot flashes, fever, decreased appetite, and diarrhoea. Psychological withdrawal symptoms commonly reported were restlessness, tension, anger, sadness, and nervousness. The average amount of the psychoactive compound, mitragynine, in a single dose of a Kratom drink was 79mg, suggesting an average daily intake of 276.5mg. Regular users who consumed ≥3 glasses Kratom per day, had higher odds of developing severe Kratom dependence, withdrawal symptoms, and inability to control Kratom craving. ConclusionsThe findings from this study show that regular Kratom use is associated with drug dependency, development of withdrawal symptoms, and craving. These symptoms become more severe with prolonged use and suggest a stronger control of the drug.

Methylnaltrexon

Chronic pain patients using opioids frequently suffer from constipation which compromises well-being. Such an opioid-induced gastro-intestinal complication can occur regularly in patients in palliative care as well as in analgesic sedated intensive care patients or during prolonged perioperative pain therapy. Discomfort and distress in the affected patients can be so severely pronounced that they would rather suffer from the pain than from the side effect of constipation. Conventional therapy can be insufficient in providing satisfactory relief of constipation, mostly because this opioid-induced bowel hypomotility can be laxative-resistant. Moreover, constipation does not decrease during the course of therapy as do other side effects. It is well known that opioid-induced constipation is mediated via activation of micro-opioid receptors in the gastrointestinal tract. Selective peripheral micro-receptor antagonists (such as methylnaltrexone, Relistor) can effectively treat opioid-induced constipation. An interference with central analgesia does not occur as the molecules cannot pass the blood-brain barrier due to their charged states. A reduction of opioid therapy or the development of withdrawal symptoms can be avoided. Studies have shown that methylnaltrexone is not only safe and efficient for chronically constipated palliative care patients but offers promising therapeutic options for further patient collectives.

Withdrawal symptoms over time among adolescents in a smoking cessation intervention: Do symptoms vary by level of nicotine dependence?

Nicotine dependence may be expressed differently in teens than in adults. Thus, it may not be sufficient to build diagnostic and cessation treatment strategies for teens based on adult-derived clinical and research data. This is the first study to prospectively examine the development of withdrawal symptoms by level of nicotine dependence among adolescent smokers. Forty-seven adolescent smokers completed nicotine withdrawal symptoms measures during 10 weeks of cessation treatment. Nicotine dependence was assessed at baseline using the mFTQ. Change in withdrawal symptoms over time by level of nicotine dependence was examined via mixed model ANOVA. Nicotine withdrawal in daily adolescent smokers was strongly and prospectively associated with the level of nicotine dependence. Craving was rated as the most problematic symptom at the baseline assessment. The results of this study may help guide the development of future research on diagnostic and cessation treatment strategies for teens.

The Role of Gateway Drugs and Psychosocial Factors in Substance Dependence in Eastern India

Western studies have identified the gateway patterns of substance use which lead the way from the so called "Soft Drugs" (like nicotine, etc.) to the "Hard Drugs" (like Opioids) [the Gateway hypothesis]. Nicotine and alcohol have been implicated as the most common initiating drugs in studies from different places, however, studies are lacking from this region. This study was designed to find the drugs of initiation and to understand the factors for initiation, maintenance, and relapse of these substances in persons dependent on them in Eastern India. Seventy subjects with ICD 10 DCR diagnosis of substance dependence admitted consecutively in Center for Addiction Psychiatry, Central Institute of Psychiatry (CIP), Ranchi, were taken up for the study after taking written informed consent. A semistructured questionnaire including the substance use part of Mini International Neuropsychiatric Inventory (MINI) was administered. Alcohol and opioids were the most common drugs of dependence but nicotine and alcohol were found to be the most common initiating drugs in both alcohol and opioid groups. Persons dependent on opioids presented earlier for treatment, with earlier development of withdrawal symptoms and having completed lesser years of formal education, and had higher monthly incomes as compared to those dependent on alcohol. The most common psychosocial factors determining initiation and maintenance were peer pressure or curiosity. If adolescents and youth can be motivated to stay away even from the "gateway drugs" by targeting common initiation factors, it may lead to delay in dependence or possibly avoidance of development of dependence.

The Efficacy of the COMFORT Scale in Assessing Optimal Sedation in Critically Ill Children Requiring Mechanical Ventilation

Sedation is often necessary to optimize care for critically ill children requiring mechanical ventilation. If too light or too deep, however, sedation can cause significant adverse reactions, making it important to assess the degree of sedation and maintain its optimal level. We evaluated the efficacy of the COMFORT scale in assessing optimal sedation in critically ill children requiring mechanical ventilation. We compared 12 month data in 21 patients (intervention group), for whom we used the pediatric intensive care unit (PICU) sedation protocol of Asan Medical Center (Seoul, Korea) and the COMFORT scale to maintain optimal sedation, with the data in 20 patients (control group) assessed before using the sedation protocol and the COMPORT scale. Compared with the control group, the intervention group showed significant decreases in the total usage of sedatives and analgesics, the duration of mechanical ventilation (11.0 days vs. 12.5 days) and PICU stay (15.0 days vs. 19.5 days), and the development of withdrawal symptoms (1 case vs. 7 cases). The total duration of sedation (8.0 days vs. 11.5 days) also tended to decrease. These findings suggest that application of protocol-based sedation with the COMPORT scale may benefit children requiring mechanical ventilation.

Alcohol Screening in the Acute Care Hospital

Many people admitted to the acute care hospital routinely use alcohol. Their patterns of drinking may vary widely from being low risk to hazardous. It is known that alcohol plays a part in the etiology of some illnesses and adds risk of further morbidity with the development of withdrawal symptoms. Conducting alcohol screening on patients admitted to the hospital cues the nurse to identify those patients in jeopardy of alcohol withdrawal syndrome. Nurses can be proactive in planning interventions for their patients. Early recognition and a timely response can facilitate healing and form an environment that is caring, protective and respectful of the patient's needs.

Use of ANAR for the therapy of opium withdrawal syndrome.

We studied the efficiency of ANAR containing antibodies to morphine (dilutions C300 and C200) in the therapy of patients with the opium withdrawal syndrome. In patients with moderate to severe forms of the opium withdrawal syndrome therapeutic activity of ANAR was comparable to that of standard symptomatic drugs. ANAR possessed vegetostabilizing, sedative, and analgetic properties. Treatment with ANAR allowed us to reduce doses of psychotropic and analgetic preparations and delay the development of withdrawal symptoms by 18-24 h.

Dosing and switching strategies for quetiapine fumarate

Background: The atypical antipsychotic agent quetiapine fumarate has demonstrated efficacy and tolerability in clinical trials in patients with chronic or subchronic exacerbations of schizophrenic symptoms. Objective: This review summarizes clinical trial data and other practical information regarding the initiation and routine administration of quetiapine. Appropriate strategies for switching from other antipsychotic agents to quetiapine are also discussed. Results: Quetiapine is an appropriate initial treatment for psychotic disturbances in patients with schizophrenia of any stage and for those in whom a therapeutic switch is indicated for clinical reasons, such as inability to tolerate the side effects of treatment. Titration to 400 mg/d is recommended using the following schedule, administered BID in divided doses: day 1, 50 mg; day 2, 100 mg; day 3, 200 mg; day 4, 300 mg; and day 5, 400 mg. In patients who respond to quetiapine, therapy should be continued at the optimal dose that maintains remission, within the range of 150 to 750 mg/d. When a change in therapy is indicated, several strategies for switching from one antipsychotic agent to another may be applied to switching to quetiapine. Whereas studies have shown that an abrupt switch to or withdrawal from quetiapine does not produce significant clinical consequences, in practice the switch should be carefully individualized to minimize the potential for psychotic relapse or development of withdrawal symptoms. Conclusions: Quetiapine has antipsychotic effects and good tolerability at doses from 150 to 750 mg/d. Patients can be switched to quetiapine and their treatment individualized to achieve the optimal therapeutic effect with a minimum of dose-limiting side effects. There are several strategies for switching to quetiapine from another antipsychotic agent that do not appear to cause significant exacerbation of psychosis or withdrawal reactions.

Nicotine withdrawal in women

Associations between self-report symptom profiles for nicotine withdrawal, personality (TPQ, EPQ-R), life-time history of psychopathology and smoking history were examined in data obtained from 553 female adult Australian twins (246 regular smokers), aged 32-48 years, who had participated in a telephone interview survey that included life-time assessments of smoking history, nicotine dependence and symptoms of withdrawal. Two hundred and two respondents were from high-risk pairs where either the respondent or the respondent's co-twin had reported a life-time history of alcohol dependence; 351 were from control pairs. Latent class analysis was used to identify subtypes ('classes') of smokers reporting similar withdrawal symptom profiles. Three major classes were identified which appeared to represent a continuum from mild to severe nicotine withdrawal. Smokers from the severe withdrawal class were best characterized by hands shaking and by the prominence of depressive features. There were marked increases in life-time alcohol dependence rates as a function of severity class. In contrast, significantly elevated rates of major depression, conduct disorder and anxiety disorder were observed only among smokers from the most severe withdrawal class. Neuroticism was the only personality factor strongly associated with the development of withdrawal symptoms.

Nicotine withdrawal in women

Associations between self-report symptom profiles for nicotine withdrawal, personality (TPQ, EPQ-R), life-time history of psychopathology and smoking history were examined in data obtained from 553 female adult Australian twins (246 regular smokers), aged 32-48 years, who had participated in a telephone interview survey that included life-time assessments of smoking history, nicotine dependence and symptoms of withdrawal. Two hundred and two respondents were from high-risk pairs where either the respondent or the respondent's co-twin had reported a life-time history of alcohol dependence; 351 were from control pairs. Latent class analysis was used to identify subtypes (‘classes’) of smokers reporting similar withdrawal symptom profiles. Three major classes were identified which appeared to represent a continuum from mild to severe nicotine withdrawal. Smokers from the severe withdrawal class were best characterized by hands shaking and by the prominence of depressive features. There mere marked increases in life-time alcohol dependence rates as a function of severity class. In contrast, significantly elevated rates of major depression, conduct disorder and anxiety disorder were observed only among smokers from the most severe withdrawal class. Neuroticism was the only personality factor strongly associated with the development of withdrawal symptoms.

Clonidinsupplementierte Analgosedierung zur postoperativen Delirprophylaxe

In an open prospective study we investigated the efficacy of the supplementation of analgosedation by clonidine. 40 patients with oesophagus malignancy and definite alcohol abuse were on respiration therapy postoperatively after having been treated with oesophago-gastro anastomoses. With regard to manifestation intensity and development of withdrawal symptoms we found that during basic medication with piritramid-diazepam continuously i.v. administered clonidine can eliminate haemodynamic and psychovegetative symptoms related to alcohol withdrawal. The clonidine group required less analgosedation. The measurement of the urinary catecholamine output showed a normalised endogenous output. As a finding of importance the gastrovolume was reduced, and the haemodynamically firm, stable and less sedated patients of the clonidine group required fewer days of respiration therapy. Hence, the hazard of aspiration pneumonia and insufficienty anastomosis was lower. Risk of bradycardia of high potential danger did not occur with a median daily dosage of 1.09 mg/d clonidine. We consider clonidine to be a potent supplement to analgosedation for the surgical patient who is at high risk of alcohol withdrawal.

Methadone Maintenance:

Since first developed by Dole and Nyswander, there have been significant changes in the clinical use of methadone, based on evaluation of the initial programs and a better understanding of the psychology and pharmacology of addictive behavior. Treatment has evolved from Dole's original concept that methadone "blockaded" the euphoric effect of heroin to current usage which reflects a greater appreciation of methadone's ability to prevent the development of withdrawal symptoms and to moderate intense affective states. The successes and limitations of methadone maintenance are best appreciated in comparison with alternative treatment modalities including therapeutic communities and detoxification. Program administrators face unique pressures because of the need to resolve the often contradictory goals of patients, staff, community groups, law enforcement officials, government regulators and funding agents. The evolution of effective treatment models has been greatly impaired by these pressures. Clinicians must become more effective leaders in helping to resolve these problems and to help formulate more rational drug abuse treatment policy.

Opiate addiction and depression — cause or effect?

The treatment of opiate addiction is a complex and often frustrating task. Opiate addiction is an illness which is subject to great prejudice and misunderstanding and opiate addicts are generally viewed by society with disdain and ostracism. It is necessary to understand the psychological and physiological forces that form the underpinnings of opiate addiction before the provider of care can transcend societal prejudices and develop an objective strategy of treatment. Such an understanding also provides the empathy necessary to relate to these patients, and coincidentally leads to some surprising speculations regarding possible roles of natural opiate systems in the brain. The purpose of this paper will be to review some of our clinical research data which have led to our structured treatment program for opiate addiction. Before proceeding to a framework for understanding opiate addiction, it is useful to examine some of the reasons why addicts are misunderstood. The recreational use of opiates seems difficult to justify in light of the perils of opiate addiction. The injection of street heroin of unknown potency can easily lead to lethal overdose. Drug-related medical illness such as malnutrition, numerous forms of hepatitis, vasculopathies, tetanus, tuberculosis and other infections, can cause morbidity or mortality. The necessity of obtaining drugs disrupts job performance and social ties, and opiates become the addicts’ pre-eminent focus. Procurement of illegal drugs is a dangerous task, exposing the addict to risks of assault, blackmail, death or incarceration at the time when judgment is often impaired by drug intoxication or abstinence symptoms. Psychiatric complications, particularly depression, can lead to prolonged suffering and even suicide. The development of withdrawal symptoms and panic are always hours away, constituting a firm reinforcement of continued addiction. Sociopathic activities, often employed to avoid withdrawal symptoms and obtain drug supplies, cause others to suffer and increase social isolation. These and other hazards associated with opiate addiction contribute to the general lack of understanding of what could motivate individuals to become or stay opiate dependent. Opiate addiction becomes more comprehensible in the light of classical conditioning theory as described by Wikler [ 11. The euphoric effect of opiates,